69, 95%CI 0.45-1.05)CONCLUSION Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.BACKGROUND In the absence of reliable data on drug-resistant TB in Eritrea, a national survey was conducted in 2018 using molecular-based methods, bypassing the need for culture.METHODS A cross-sectional study was conducted in all 77 TB microscopy centres in the country. All 629 newly registered sputum smear-positive pulmonary TB patients were enrolled over 12 months. Sputum samples were tested using the Xpert® MTB/RIF assay and targeted next-generation sequencing (Deeplex Myc-TB) to identify resistance and explore the phylogenetics of Mycobacterium tuberculosis complex strains.RESULTS Drug resistance profiles were obtained for 555 patients (502 new, 53 previously treated). The prevalence of rifampicin-resistant TB (RR-TB) was respectively 2.0% and 7.6% among new and previously treated cases. All RR-TB isolates that were susceptible to isoniazid displayed a phylogenetic marker conferring capreomycin resistance, confirming circulation of a previously described resistant TB sub-lineage in the Horn of Africa. Only one case of fluoroquinolone resistance was detected.CONCLUSION The prevalence of rifampicin resistance among TB patients is encouragingly low. The scarcity of fluoroquinolone resistance bodes well for the success of the recommended all-oral treatment regimen. Surveillance based on molecular approaches enables a reliable estimation of the burden of resistance and can be used to guide appropriate treatment and care.BACKGROUND Anti-TB drugs dosing based on weight alone may contribute to suboptimal drug concentrations and poor treatment outcomes in malnourished children. We examined the effect of malnutrition on the pharmacokinetics (PK) of first-line anti-TB drugs in children.METHODS Drug concentrations were measured in Ghanaian children during the intensive phase of TB treatment. Weight-for-age (WFA), height-for-age (HFA), weight-for-height (WFH) and body mass index-for-age (BFA) were calculated and children with Z-scores less then -2 SD (standard deviations) were considered as having malnutrition. PK differences of anti-TB drugs were compared by nutritional status.RESULTS Of 100 participants, 24/48 (50.0%) of those younger than 5 years had wasting, 58/86 (67.4%) were underweight, and 56/99 (56.6%) had stunting; 22/51 (43.1%) children aged ?5 years had low BFA. Children with stunting were more likely than controls to have lower mean peak concentration (Cmax) and area under the curve (AUC0-8h) of rifampin (RIF) and pyrazinamide (PZA), as well as a higher frequency of Cmax below the normal range. https://www.selleckchem.com/products/H-89-dihydrochloride.html Wasting and underweight were associated with lower mean ethambutol (EMB) Cmax and AUC0-8h.CONCLUSIONS The current WHO-recommended dosages were associated with lower plasma exposure of RIF, PZA and EMB in children with stunting, wasting and underweight. Anti-TB drugs dosing models for children may need to include height.BACKGROUND Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE To examine the associations between adipokines and the risk of active TB.METHODS In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.BACKGROUND The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic review evaluates the incidence of ototoxicity among patients treated for MDR-TB, and the evidence for routine audiometric monitoring to mitigate its severity.METHODS Studies of ototoxicity among patients with MDR-TB were identified from six databases PubMed, MEDLINE, Web of Science, Embase, SCOPUS and the Cochrane Library. Meta-analyses were performed to determine the overall incidence of hearing loss, tinnitus and vertigo. The incidence of hearing loss was further stratified by country income status and the injectable agent used during treatment.RESULTS Among 64 studies from 25 countries including 12?793 patients, 28.3% (95%CI 23.4-33.1) of patients treated with injectables reported hearing loss. Tinnitus and vertigo were experienced by respectively 14.5% (95%CI 10.3-18.7) and 8.1% (95%CI 4.7-11.6) of patients. The incidence of hearing loss was highest among patients treated with amikacin (33.4%, 95%CI 18.2-48.6), and lowest among those treated with capreomycin (2.0%, 95%CI 0-5.5). We found that audiometry was widely used as a method of evaluating hearing loss, and was feasible in a wide range of settings.CONCLUSION Injectable antibiotics contribute to significant morbidity in patients with MDR-TB. In settings where they are used, routine audiometric monitoring is recommended to prevent irreversible damage.OBJECTIVE To determine prevalence of and risk factors for respiratory symptoms in an adult urban Pakistani population.METHODS We conducted a multi-stage, community-based, cross-sectional survey from May 2014 to August 2015, comprising 1629 adults from 75 random clusters in Karachi using questionnaire-based interviews.RESULTS Around 60% of participants were females and 43% belonged to the &gt;37 years age group. At least one respiratory symptom was reported by 37.5% of participants. Breathlessness was the most common symptom (25.2%, 95%CI 23.1-27.3), followed by acute wheeze (10.1%, 95%CI 8.7-11.7). Multivariable models revealed that males and those aged &gt;37 years were more likely to report acute and chronic phlegm and bronchitis, and breathlessness. Participants with a higher level of education were less likely to report acute and chronic cough. Participants with &gt;5 years pack-years of smoking were more likely to report acute and chronic cough and breathlessness. Other risk factors included passive smoking, regular use of air conditioning and mosquito coils, wet spots and mould in the house, and exposure to dusty jobs.